EP2323625B1 - New composition for the treatment of ecchymotic pigmentations - Google Patents
New composition for the treatment of ecchymotic pigmentations Download PDFInfo
- Publication number
- EP2323625B1 EP2323625B1 EP09740732.4A EP09740732A EP2323625B1 EP 2323625 B1 EP2323625 B1 EP 2323625B1 EP 09740732 A EP09740732 A EP 09740732A EP 2323625 B1 EP2323625 B1 EP 2323625B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- lactoferrin
- composition
- treatment
- present
- vitamin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000203 mixture Substances 0.000 title claims description 61
- 238000011282 treatment Methods 0.000 title claims description 23
- 208000012641 Pigmentation disease Diseases 0.000 title claims description 6
- 230000019612 pigmentation Effects 0.000 title claims description 6
- 108010063045 Lactoferrin Proteins 0.000 claims description 30
- 102000010445 Lactoferrin Human genes 0.000 claims description 30
- 235000021242 lactoferrin Nutrition 0.000 claims description 30
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 claims description 29
- 229940078795 lactoferrin Drugs 0.000 claims description 29
- 238000009825 accumulation Methods 0.000 claims description 18
- 239000000126 substance Substances 0.000 claims description 15
- 229910001385 heavy metal Inorganic materials 0.000 claims description 13
- 239000004480 active ingredient Substances 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 9
- 206010040829 Skin discolouration Diseases 0.000 claims description 8
- 230000000699 topical effect Effects 0.000 claims description 6
- 210000000170 cell membrane Anatomy 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 239000002245 particle Substances 0.000 claims description 4
- 230000007170 pathology Effects 0.000 claims 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 27
- 229910052751 metal Inorganic materials 0.000 description 17
- 239000002184 metal Substances 0.000 description 17
- 230000035508 accumulation Effects 0.000 description 16
- 238000009472 formulation Methods 0.000 description 16
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 14
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 14
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 14
- 229910052742 iron Inorganic materials 0.000 description 14
- 150000002739 metals Chemical class 0.000 description 12
- 230000009471 action Effects 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 235000018102 proteins Nutrition 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- GNKZMNRKLCTJAY-UHFFFAOYSA-N 4'-Methylacetophenone Chemical compound CC(=O)C1=CC=C(C)C=C1 GNKZMNRKLCTJAY-UHFFFAOYSA-N 0.000 description 7
- 241001310324 Cetraria islandica Species 0.000 description 7
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 7
- PHOQVHQSTUBQQK-SQOUGZDYSA-N D-glucono-1,5-lactone Chemical compound OC[C@H]1OC(=O)[C@H](O)[C@@H](O)[C@@H]1O PHOQVHQSTUBQQK-SQOUGZDYSA-N 0.000 description 7
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 description 7
- 240000000366 Melilotus officinalis Species 0.000 description 7
- 235000017822 Melilotus officinalis Nutrition 0.000 description 7
- IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 description 7
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 7
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 7
- 244000269722 Thea sinensis Species 0.000 description 7
- 229930003268 Vitamin C Natural products 0.000 description 7
- 229930003427 Vitamin E Natural products 0.000 description 7
- 240000006365 Vitis vinifera Species 0.000 description 7
- 235000014787 Vitis vinifera Nutrition 0.000 description 7
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 7
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 7
- 235000012209 glucono delta-lactone Nutrition 0.000 description 7
- 229960003681 gluconolactone Drugs 0.000 description 7
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 7
- 235000002532 grape seed extract Nutrition 0.000 description 7
- 235000009569 green tea Nutrition 0.000 description 7
- -1 iron ion Chemical class 0.000 description 7
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 7
- AGBQKNBQESQNJD-UHFFFAOYSA-M lipoate Chemical compound [O-]C(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-M 0.000 description 7
- 235000019136 lipoic acid Nutrition 0.000 description 7
- 229940068041 phytic acid Drugs 0.000 description 7
- 235000002949 phytic acid Nutrition 0.000 description 7
- 239000000467 phytic acid Substances 0.000 description 7
- 235000005875 quercetin Nutrition 0.000 description 7
- 229960001285 quercetin Drugs 0.000 description 7
- 208000017520 skin disease Diseases 0.000 description 7
- 229960002663 thioctic acid Drugs 0.000 description 7
- 231100000331 toxic Toxicity 0.000 description 7
- 230000002588 toxic effect Effects 0.000 description 7
- 235000019154 vitamin C Nutrition 0.000 description 7
- 239000011718 vitamin C Substances 0.000 description 7
- 235000019165 vitamin E Nutrition 0.000 description 7
- 229940046009 vitamin E Drugs 0.000 description 7
- 239000011709 vitamin E Substances 0.000 description 7
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 6
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- LUKBXSAWLPMMSZ-UHFFFAOYSA-N resveratrol Chemical compound C1=CC(O)=CC=C1C=CC1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-UHFFFAOYSA-N 0.000 description 6
- 210000003491 skin Anatomy 0.000 description 6
- 235000019155 vitamin A Nutrition 0.000 description 6
- 239000011719 vitamin A Substances 0.000 description 6
- 229940045997 vitamin a Drugs 0.000 description 6
- 102000008857 Ferritin Human genes 0.000 description 5
- 108050000784 Ferritin Proteins 0.000 description 5
- 238000008416 Ferritin Methods 0.000 description 5
- 239000013522 chelant Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 230000009920 chelation Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 3
- 239000002738 chelating agent Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 230000037365 barrier function of the epidermis Effects 0.000 description 2
- 231100000693 bioaccumulation Toxicity 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000002655 chelation therapy Methods 0.000 description 2
- 201000002816 chronic venous insufficiency Diseases 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 150000003278 haem Chemical class 0.000 description 2
- 230000009931 harmful effect Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000009103 reabsorption Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000007632 sclerotherapy Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 201000002282 venous insufficiency Diseases 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 description 1
- DFJACSJACSDRSG-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;calcium;sodium Chemical compound [Na].[Na].[Ca].OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O DFJACSJACSDRSG-UHFFFAOYSA-N 0.000 description 1
- 241000195940 Bryophyta Species 0.000 description 1
- 241000040710 Chela Species 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 208000031856 Haemosiderosis Diseases 0.000 description 1
- 208000018565 Hemochromatosis Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010027439 Metal poisoning Diseases 0.000 description 1
- 101710093543 Probable non-specific lipid-transfer protein Proteins 0.000 description 1
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 description 1
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 description 1
- 208000000558 Varicose Ulcer Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000009102 absorption Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910052768 actinide Inorganic materials 0.000 description 1
- 150000001255 actinides Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229910052785 arsenic Inorganic materials 0.000 description 1
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000007321 biological mechanism Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 210000003850 cellular structure Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229930002875 chlorophyll Natural products 0.000 description 1
- 235000019804 chlorophyll Nutrition 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- WQABCVAJNWAXTE-UHFFFAOYSA-N dimercaprol Chemical compound OCC(S)CS WQABCVAJNWAXTE-UHFFFAOYSA-N 0.000 description 1
- 229960001051 dimercaprol Drugs 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 235000020256 human milk Nutrition 0.000 description 1
- 210000004251 human milk Anatomy 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052747 lanthanoid Inorganic materials 0.000 description 1
- 150000002602 lanthanoids Chemical class 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229910052752 metalloid Inorganic materials 0.000 description 1
- 150000002738 metalloids Chemical class 0.000 description 1
- 235000011929 mousse Nutrition 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 229940042880 natural phospholipid Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 210000001819 pancreatic juice Anatomy 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229960001639 penicillamine Drugs 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000021283 resveratrol Nutrition 0.000 description 1
- 229940016667 resveratrol Drugs 0.000 description 1
- 210000002955 secretory cell Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 210000001138 tear Anatomy 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/40—Transferrins, e.g. lactoferrins, ovotransferrins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
Definitions
- the present invention concerns a pharmaceutical, dermatological or cosmetic preparation based on chelating substances for the treatment of disorders characterised by accumulation of heavy metals, in particular for the treatment of ecchymotic pigmentations.
- heavy metals indicates some metals and metalloids that are toxic for the organism even at low concentrations. Therefore the term “heavy metals” generally defines all those metals with high atomic mass and high density such as copper, lead, mercury and zinc, and in general d-block metals, lanthanoids and actinoids. Other metals, even if not classified as heavy metals and even if they do not show particular toxicity per se and at times are even essential for living organisms, if accumulated in the organism, can produce serious toxic effects.
- an excess quantity of iron accumulated in the organism can result in high toxicity, since the free ions of the iron react with the peroxides and produce free radicals which are very reactive and can therefore cause damage to the DNA, to the proteins, lipids and other cell components. Consequently, an accumulation of iron in the cells can cause substantial damage to the organism.
- the metals most studied and best-known for the above-mentioned problems and for problems of atmospheric pollution are lead, nickel, cadmium, mercury, arsenic, iron and chromium.
- Living organisms are very sensitive to heavy metals and metals in general which are toxic above a very low concentration threshold (depending on the element).
- chelation is a chemical reaction in which, usually, a metal atom is bound by a reagent called chelant by means of more than one bond, for example a coordinate type bond.
- a reagent called chelant by means of more than one bond, for example a coordinate type bond.
- the structure of the resulting compound constitutes a particularly stable complex in which the central atom is encircled pincer-like by the chelant, as if it were clenched between the chela of a crab (hence the term chelation).
- chelants refers to the group of substances used in therapy to bind other substances present in pathological concentrations in the organism, thus favouring elimination via the normal excretion routes.
- desferroxamine is used to eliminate pathological deposits of iron (haemosiderosis and haemochromatosis).
- Other chelants dimercaprol or BAL; disodium-calcium-ethylendiaminetetracetic acid; penicillamine are used for acute or chronic metal poisoning (lead in particular).
- the ideal chelating agent should have the following characteristics:
- US 2004/0214750 discloses lactoferrin formulations for healing skin conditions in humans.
- lactoferrin can play an important role in medical practice, but the problems connected with its chemical and physical nature limit its use.
- the object of the present invention is to provide a composition, in particular a composition based on natural chelating substances which consists of lactoferrin carried by association with nanolipids which are particles having a structure analogous to the cell membranes, with a diameter of less than 250 nm as active ingredient, for use in the treatment of skin disorders characterised by accumulation of heavy metals.
- a further object of the present invention is to provide a pharmaceutical composition for the treatment of skin disorders such as ecchymotic lesions.
- a further object of the present invention is to provide a pharmaceutical composition for topical use for the treatment of cutaneous dyschromia due to accumulation of haemosiderin or ferritin.
- a further object of the invention is also to provide a process for preparing the composition.
- a further object of the invention is to provide a composition that can have a pharmaceutical use.
- compositions based on natural chelating substances which comprises carried lactoferrin, in addition to the usual excipients and additives.
- lactoferrin according to the invention, is carried in nanolipids .
- the present invention overcomes the limits of the known art since it exploits the chelating properties of lactoferrin not, for example, as a support for antibiotic treatment but as an active ingredient for the treatment of skin disorders characterised by accumulation of heavy metals and in particular in the treatment of skin disorders such as ecchymotic lesions.
- composition subject of the present invention is advantageously used for the treatment of skin disorders characterised by accumulation of heavy metals, and in particular for treatment of the cutaneous dyschromia correlated with it.
- composition subject of the invention is advantageously used for the treatment of ecchymotic pigmentations of various types.
- composition can be used in the pharmaceutical, cosmetic or cosmeceutic sector, in particular for topical use.
- the present invention therefore concerns a formulation or composition based on natural chelating substances, in which one of the essential components is represented by lactoferrin associated with nanolipids.
- the present invention also concerns a pharmaceutical formulation based on natural chelating substances for the treatment of skin disorders characterised by accumulation of heavy metals if necessary with the addition of salts and/or pharmacologically acceptable additives.
- compositions or formulation indicates the compositions or formulations that comprise natural chelating substances, in particular lactoferrin associated with nanolipids as active ingredient.
- addition of pharmaceutically acceptable salts refers to all those salts which from the biological, preparation and formulation point of view are compatible with pharmaceutical practice.
- composition subject of the invention is advantageously used for the preparation of a medicament for the treatment of skin dyschromias due to the accumulation of haemosiderin or ferritin.
- the formulations or compositions according to the invention are suitable for topical administration of the active ingredients.
- the topical formulations for the treatment of skin disorders characterised by accumulation of metals are, for example, creams, lotions, mousses, sprays, emulsions, gels, ointments and similar compatible with the preparation according to the methods commonly known in the state of the art.
- the formulation according to the invention comprises lactoferrin as essential active ingredient associated with nanolipids in a concentration range of between 1% and 20%, preferably between 3% and 12%, even more preferably between 5% and 9% w/w of the total composition.
- the lactoferrin associated with nanolipids is present in a concentration of 6% w/w of the total composition.
- nanolipids refers to particles with structure analogous to the cell membranes, in particular those preferably with a diameter of less than 250 nm.
- They consist mainly of natural phospholipids arranged in a double layer.
- the preparation is carried out in equipped laboratories, with suitable instruments, using ultrasound dispersion technique and homogenisation, under pressure and at controlled temperature.
- the combination, according to the invention, of the protein lactoferrin in nanolipids overcomes the limits of the known art since the active ingredient, in this case the lactoferrin, is incorporated in the nanoparticles of the phospholipids, thus increasing absorption, penetration and diffusion of the protein molecules incorporated and furthermore protecting the protein from possible denaturation.
- the protein carried in this way is therefore able to overcome the barrier of the epidermis and come into contact with the metals, in particular with the iron, accumulated in the tissues below and responsible for the toxic and harmful effect to be reduced or eliminated.
- the lactoferrin carried in this way reaches, in a large quantity and in an integral form, the accumulations of said metal and is therefore able to perform its chelating action, withdrawing iron and removing the cause of the damage.
- the formulations or compositions according to the present invention comprise lactoferrin as active ingredient associated with nanolipids from 1% to 20%, each of the above-mentioned percentages being expressed in w/w of the total composition.
- the subject of the present invention is therefore a pharmaceutical composition having chelating and clarifying action for the treatment of skin impurities and blemishes connected with the accumulation of heavy metals and metals in general, characterised by optimal pharmacokinetic parameters and bioavailability.
- the composition can be used for example for the treatment of skin impurities and dyschromia caused by harmful waste substances, ecchymotic pigmentation and toxic accumulation.
- Said composition ensures an effective depurative and lightening effect due to the chelating action of its components, in particular due to the action performed by the lactoferrin carried in nanolipids. Said chelating action ensures rapid elimination of the exogenous and endogenous toxic accumulations.
- composition according to the invention due to its surprising characteristics, removes the dermal deposit of heavy metals even in particular conditions, for example conditions such that the accumulation of said metals is consequent upon the stimulation and production of free radicals which favour and accelerate ageing of the dermal-epidermal structures.
- composition according to the invention is also particularly advantageous in reduction of the brown colouring caused by hyperaccumulation of ferritin in chronic venous insufficiency and after sclerotherapy.
- composition subject of the present invention could also be used in the treatment of venous ulcers.
- the formulation for topical use according to the invention can be used even several times a day, preferably twice a day, in the space of 24 hours.
- the composition subject of the present invention therefore contains a mixture of chelating agents all of natural extraction, selective and completely nontoxic.
- the most effective active ingredient is the lactoferrin which, as already mentioned, is a multifunctional protein present in mother's milk, for example.
- lactoferrin needs to be appropriately carried in order to best perform its chelating action.
- the lactoferrin passes through the epidermal barrier in fairly low concentrations and, consequently, performs its chelating action with unsatisfactory results.
- it passes through the epidermal barrier in high concentrations and the chelating action is effectively performed, with immediate and surprising results.
- suitable carriers which, again according to the present invention, have been identified for example in nanolipids and sulphuric substances which represent factors that increase cell permeability. Said carriers have permitted the development of a component of the composition, i.e. carried lactoferrin, which provides surprising results in terms of efficacy of the composition in promoting the reabsorption of waste substances, in particular metal ions, from the skin.
- the toxic accumulations are rapidly eliminated and, by removal of the iron ion, the formation of free radicals is drastically and significantly reduced with consequent reduction in the oxidative stress responsible for ageing of the skin.
- the selective chelating action exercised by the composition subject of the present invention on the deposits of haemosiderin and ferritin makes the composition particularly effective and active in reabsorption of the ecchymotic pigmentations caused by accidental trauma or surgery.
- the high selectivity and high bioavailability of the composition subject of the invention mean that it can be advantageously used for the treatment of cutaneous dyschromias resulting from sclerotherapy and in dyschromias caused by chronic venous insufficiency.
- a further subject of the present invention is the process for the preparation of said composition.
- said aqueous step a) is preferably performed at a temperature of approximately 40°C.
- at least one of the following compounds is mixed: phytic acid, lipoic acid, vitamin E, vitamin A, vitamin C, quercetin, reduced L-glutathione, cetraria islandica, green tea, vitis vinifera (resveratrol) gluconolactone, M.S.M., melilot.
- step a) at least two of the following compounds are preferably mixed: phytic acid, lipoic acid, vitamin E, vitamin A, vitamin C, quercetin, reduced L-glutathione, cetraria islandica, green tea, vitis vinifera (resveratrol) gluconolactone, M.S.M., melilot and even more preferably the following components are mixed: phytic acid, lipoic acid, vitamin E, vitamin A, vitamin C, quercetin, reduced L-glutathione, cetraria islandica, green tea, vitis vinifera (titred in resveratrol) gluconolactone, M.S.M., melilot.
- Said step b), considered essential for the success of the process subject of the invention, is performed at a temperature of approximately 70°C.
- the mixed excipients suitable for the formulation according to the known technique are added.
- said fatty step b) can be performed as a first phase of said process or, alternatively, as a step subsequent to said aqueous step a).
- Said process furthermore consists of a cooling step c) also considered essential, which is preferably performed at a temperature between 25 and 30°C.
- a cooling step c) also considered essential, which is preferably performed at a temperature between 25 and 30°C.
- the lactoferrin associated with nanolipids is added to the reaction mixture.
- step c) is performed at a temperature of 30°.
- Suitable solutions are added to the composition obtained according to said steps b) and c) or alternatively a), b) and c) to obtain a composition with a pH between 5 and 6, preferably 6.
- the formulation according to the present invention comprises: lactoferrin associated with nanolipids 6%, phytic acid 3%, lipoic acid 2.5 %, vitamin E 1%, vitamin A 1%, vitamin C 2%, quercetin 0.09%, reduced L-glutathione 3%, cetraria islandica 2%, green tea 2.8%, vitis vinifera (resveratrol) 3%, gluconolactone 4%, M.S.M. 8%, melilot 0.1%, excipients and water to 100%.
- aqueous step a performed at a temperature of approximately 40°C, the following compounds are mixed together: phytic acid, lipoic acid, vitamin E, vitamin A, vitamin C, quercetin, reduced L-glutathione, cetraria islandica, green tea, vitis vinifera (resveratrol), gluconolactone, M.S.M., melilot.
- At least two of the following compounds phytic acid, lipoic acid, vitamin E, vitamin A, vitamin C, quercetin, reduced L-glutathione, cetraria islandica, green tea, vitis vinifera (resveratrol), gluconolactone, M.S.M., melilot and even more preferably the following phytic acid, lipoic acid, vitamin E, vitamin A, vitamin C, quercetin, reduced L-glutathione, cetraria islandica, green tea, vitis vinifera (resveratrol), gluconolactone, M.S.M., melilot.
- Step a) is then followed by the fatty step b) which is performed at a temperature of approximately 70°C. During this phase the excipients suited to the formulation according to the known art are added to the reaction mixture.
- step c The last step in the process, step c), is the cooling step, performed at a temperature of approximately 30°C.
- step c) the lactoferrin associated with nanolipids is added to the reaction mixture as obtained from the preceding steps a) and b).
- the resulting final composition is a cream with pH of 6, after the addition of an appropriate quantity of triethanolamine.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Dispersion Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cosmetics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Description
- The present invention concerns a pharmaceutical, dermatological or cosmetic preparation based on chelating substances for the treatment of disorders characterised by accumulation of heavy metals, in particular for the treatment of ecchymotic pigmentations.
- The term "heavy metals" indicates some metals and metalloids that are toxic for the organism even at low concentrations. Therefore the term "heavy metals" generally defines all those metals with high atomic mass and high density such as copper, lead, mercury and zinc, and in general d-block metals, lanthanoids and actinoids. Other metals, even if not classified as heavy metals and even if they do not show particular toxicity per se and at times are even essential for living organisms, if accumulated in the organism, can produce serious toxic effects.
- For example, an excess quantity of iron accumulated in the organism can result in high toxicity, since the free ions of the iron react with the peroxides and produce free radicals which are very reactive and can therefore cause damage to the DNA, to the proteins, lipids and other cell components. Consequently, an accumulation of iron in the cells can cause substantial damage to the organism.
- In general, the metals most studied and best-known for the above-mentioned problems and for problems of atmospheric pollution are lead, nickel, cadmium, mercury, arsenic, iron and chromium.
- Living organisms are very sensitive to heavy metals and metals in general which are toxic above a very low concentration threshold (depending on the element).
- The origin of their toxicity lies in the fact that these metals tend to accumulate in the tissues, and are therefore bioaccumulative.
- It is also known that chelation is a chemical reaction in which, usually, a metal atom is bound by a reagent called chelant by means of more than one bond, for example a coordinate type bond. The structure of the resulting compound constitutes a particularly stable complex in which the central atom is encircled pincer-like by the chelant, as if it were clenched between the chela of a crab (hence the term chelation).
- In biology, for example, by means of chelation haemoglobin binds iron and chlorophyll binds magnesium. In medicine chelation is exploited in chelation therapy for the treatment of certain intoxications due to the accumulation of metals in the organism: once chelated, the metal loses its characteristics (and therefore any toxicity) but above all it can be more easily eliminated together with the chelant, solving the problem of bioaccumulation.
- In medical practice therefore, the term chelants refers to the group of substances used in therapy to bind other substances present in pathological concentrations in the organism, thus favouring elimination via the normal excretion routes. Among the best-known, desferroxamine is used to eliminate pathological deposits of iron (haemosiderosis and haemochromatosis). Other chelants (dimercaprol or BAL; disodium-calcium-ethylendiaminetetracetic acid; penicillamine) are used for acute or chronic metal poisoning (lead in particular).
- Although chelation therapy is useful and effective (and in some cases irreplaceable), it has numerous drawbacks connected with the pharmacokinetic properties of the chelating agents. The ideal chelating agent should have the following characteristics:
- high selectivity towards the metal to be chelated to reduce side effects ability to reduce the metal deposit level
- ability to prevent, avoid or reduce induced cell damage
- non-toxicity
- There is the need to identify chelating molecules that overcome the limits of the known art.
- A protein, lactoferrin, with multiple bioactive properties linked to its ability to chelate iron, has been well-known for some time and described in the literature. It is an endogenous natural chelant and is involved in numerous biological mechanisms. It is a basic protein belonging to the family of the non-haem ferritins, i.e. without the haem group (iron-chelating polypeptide). These proteins are able to bind the iron with neutral or alkaline pH and release it with acid pH. They are proteins synthesised by particular exocrine structures such as the mammary gland cells and other secretory cells, for example, tears, sweat, bile, seminal liquid and pancreatic juice. Lactoferrin is accumulated in granulocytes and in practice is produced by the glands of all mammals.
-
US 2004/0214750 discloses lactoferrin formulations for healing skin conditions in humans. - It acts by binding to and absorbing iron, a fundamental substance for the nourishment of bacteria which die when deprived of their cofactor. This mechanism is now used or exploited in pharmacology in the integration or association of antimetabolites (antibiotics) with the lactoferrins. In fact the bacteria, deprived of iron, are forced to abandon the colonies which often tend to form, thus becoming more vulnerable to pharmacological treatment.
- It is therefore clear that lactoferrin can play an important role in medical practice, but the problems connected with its chemical and physical nature limit its use.
- The object of the present invention is to provide a composition, in particular a composition based on natural chelating substances which consists of lactoferrin carried by association with nanolipids which are particles having a structure analogous to the cell membranes, with a diameter of less than 250 nm as active ingredient, for use in the treatment of skin disorders characterised by accumulation of heavy metals.
- A further object of the present invention is to provide a pharmaceutical composition for the treatment of skin disorders such as ecchymotic lesions.
- A further object of the present invention is to provide a pharmaceutical composition for topical use for the treatment of cutaneous dyschromia due to accumulation of haemosiderin or ferritin.
- A further object of the invention is also to provide a process for preparing the composition.
- A further object of the invention is to provide a composition that can have a pharmaceutical use.
- These and further objects and relative advantages which will be better clarified by the following description are achieved by a composition based on natural chelating substances which comprises carried lactoferrin, in addition to the usual excipients and additives.
- In particular lactoferrin, according to the invention, is carried in nanolipids .
- The present invention overcomes the limits of the known art since it exploits the chelating properties of lactoferrin not, for example, as a support for antibiotic treatment but as an active ingredient for the treatment of skin disorders characterised by accumulation of heavy metals and in particular in the treatment of skin disorders such as ecchymotic lesions.
- The composition subject of the present invention is advantageously used for the treatment of skin disorders characterised by accumulation of heavy metals, and in particular for treatment of the cutaneous dyschromia correlated with it.
- More specifically, the composition subject of the invention is advantageously used for the treatment of ecchymotic pigmentations of various types.
- The composition can be used in the pharmaceutical, cosmetic or cosmeceutic sector, in particular for topical use.
- The present invention therefore concerns a formulation or composition based on natural chelating substances, in which one of the essential components is represented by lactoferrin associated with nanolipids.
- The present invention also concerns a pharmaceutical formulation based on natural chelating substances for the treatment of skin disorders characterised by accumulation of heavy metals if necessary with the addition of salts and/or pharmacologically acceptable additives.
- The term "pharmaceutical composition or formulation" indicates the compositions or formulations that comprise natural chelating substances, in particular lactoferrin associated with nanolipids as active ingredient.
- The term "addition of pharmaceutically acceptable salts" here refers to all those salts which from the biological, preparation and formulation point of view are compatible with pharmaceutical practice.
- In particular, the composition subject of the invention is advantageously used for the preparation of a medicament for the treatment of skin dyschromias due to the accumulation of haemosiderin or ferritin.
- The formulations or compositions according to the invention are suitable for topical administration of the active ingredients. The topical formulations for the treatment of skin disorders characterised by accumulation of metals are, for example, creams, lotions, mousses, sprays, emulsions, gels, ointments and similar compatible with the preparation according to the methods commonly known in the state of the art.
- The formulation according to the invention comprises lactoferrin as essential active ingredient associated with nanolipids in a concentration range of between 1% and 20%, preferably between 3% and 12%, even more preferably between 5% and 9% w/w of the total composition.
- Preferably, in the formulation according to the invention, the lactoferrin associated with nanolipids is present in a concentration of 6% w/w of the total composition.
- The term "nanolipids" refers to particles with structure analogous to the cell membranes, in particular those preferably with a diameter of less than 250 nm.
- They consist mainly of natural phospholipids arranged in a double layer.
- The preparation is carried out in equipped laboratories, with suitable instruments, using ultrasound dispersion technique and homogenisation, under pressure and at controlled temperature.
- The combination, according to the invention, of the protein lactoferrin in nanolipids, overcomes the limits of the known art since the active ingredient, in this case the lactoferrin, is incorporated in the nanoparticles of the phospholipids, thus increasing absorption, penetration and diffusion of the protein molecules incorporated and furthermore protecting the protein from possible denaturation.
- The protein carried in this way is therefore able to overcome the barrier of the epidermis and come into contact with the metals, in particular with the iron, accumulated in the tissues below and responsible for the toxic and harmful effect to be reduced or eliminated.
- In the case of the iron in particular, the lactoferrin carried in this way reaches, in a large quantity and in an integral form, the accumulations of said metal and is therefore able to perform its chelating action, withdrawing iron and removing the cause of the damage.
- The formulations or compositions according to the present invention comprise lactoferrin as active ingredient associated with nanolipids from 1% to 20%, each of the above-mentioned percentages being expressed in w/w of the total composition. The subject of the present invention is therefore a pharmaceutical composition having chelating and clarifying action for the treatment of skin impurities and blemishes connected with the accumulation of heavy metals and metals in general, characterised by optimal pharmacokinetic parameters and bioavailability.
- The composition can be used for example for the treatment of skin impurities and dyschromia caused by harmful waste substances, ecchymotic pigmentation and toxic accumulation. Said composition ensures an effective depurative and lightening effect due to the chelating action of its components, in particular due to the action performed by the lactoferrin carried in nanolipids. Said chelating action ensures rapid elimination of the exogenous and endogenous toxic accumulations.
- The composition according to the invention, due to its surprising characteristics, removes the dermal deposit of heavy metals even in particular conditions, for example conditions such that the accumulation of said metals is consequent upon the stimulation and production of free radicals which favour and accelerate ageing of the dermal-epidermal structures.
- Use of the composition according to the invention is also particularly advantageous in reduction of the brown colouring caused by hyperaccumulation of ferritin in chronic venous insufficiency and after sclerotherapy.
- The composition subject of the present invention could also be used in the treatment of venous ulcers.
- The formulation for topical use according to the invention can be used even several times a day, preferably twice a day, in the space of 24 hours.
- All the concentrations indicated in the present application are considered as a w/w percentage of each of the active ingredients of the total formulation/composition.
- The composition subject of the present invention therefore contains a mixture of chelating agents all of natural extraction, selective and completely nontoxic. In particular, the most effective active ingredient is the lactoferrin which, as already mentioned, is a multifunctional protein present in mother's milk, for example. It has been found, however, according to the present invention, that lactoferrin needs to be appropriately carried in order to best perform its chelating action. In fact, in the absence of a suitable carrier, the lactoferrin passes through the epidermal barrier in fairly low concentrations and, consequently, performs its chelating action with unsatisfactory results. When appropriately carried according to the invention, on the other hand, it passes through the epidermal barrier in high concentrations and the chelating action is effectively performed, with immediate and surprising results. It is naturally important to choose suitable carriers which, again according to the present invention, have been identified for example in nanolipids and sulphuric substances which represent factors that increase cell permeability. Said carriers have permitted the development of a component of the composition, i.e. carried lactoferrin, which provides surprising results in terms of efficacy of the composition in promoting the reabsorption of waste substances, in particular metal ions, from the skin.
- Using the composition according to the invention, therefore, the toxic accumulations are rapidly eliminated and, by removal of the iron ion, the formation of free radicals is drastically and significantly reduced with consequent reduction in the oxidative stress responsible for ageing of the skin. Furthermore, the selective chelating action exercised by the composition subject of the present invention on the deposits of haemosiderin and ferritin makes the composition particularly effective and active in reabsorption of the ecchymotic pigmentations caused by accidental trauma or surgery. The high selectivity and high bioavailability of the composition subject of the invention mean that it can be advantageously used for the treatment of cutaneous dyschromias resulting from sclerotherapy and in dyschromias caused by chronic venous insufficiency.
- A further subject of the present invention is the process for the preparation of said composition.
- Said process is characterised by the presence of three different steps, which can be identified as follows:
- a) aqueous step
- b) fatty step
- c) cooling step.
- In particular said aqueous step a) is preferably performed at a temperature of approximately 40°C. In an embodiment not according to the claims, in said step a) at least one of the following compounds is mixed: phytic acid, lipoic acid, vitamin E, vitamin A, vitamin C, quercetin, reduced L-glutathione, cetraria islandica, green tea, vitis vinifera (resveratrol) gluconolactone, M.S.M., melilot.
- Again not according to the claims, in said step a) at least two of the following compounds are preferably mixed: phytic acid, lipoic acid, vitamin E, vitamin A, vitamin C, quercetin, reduced L-glutathione, cetraria islandica, green tea, vitis vinifera (resveratrol) gluconolactone, M.S.M., melilot and even more preferably the following components are mixed: phytic acid, lipoic acid, vitamin E, vitamin A, vitamin C, quercetin, reduced L-glutathione, cetraria islandica, green tea, vitis vinifera (titred in resveratrol) gluconolactone, M.S.M., melilot.
- Said step b), considered essential for the success of the process subject of the invention, is performed at a temperature of approximately 70°C. Preferably in said step b), or fatty step, the mixed excipients suitable for the formulation according to the known technique are added.
- According to the present invention, said fatty step b) can be performed as a first phase of said process or, alternatively, as a step subsequent to said aqueous step a).
- Said process furthermore consists of a cooling step c) also considered essential, which is preferably performed at a temperature between 25 and 30°C. In particular, during said step c), the lactoferrin associated with nanolipids is added to the reaction mixture.
- Preferably said step c) is performed at a temperature of 30°.
- Suitable solutions, preferably triethanolamine, are added to the composition obtained according to said steps b) and c) or alternatively a), b) and c) to obtain a composition with a pH between 5 and 6, preferably 6.
- The formulation according to the present invention comprises: lactoferrin associated with nanolipids 6%, phytic acid 3%, lipoic acid 2.5 %, vitamin E 1%, vitamin A 1%, vitamin C 2%, quercetin 0.09%, reduced L-glutathione 3%, cetraria islandica 2%, green tea 2.8%, vitis vinifera (resveratrol) 3%, gluconolactone 4%, M.S.M. 8%, melilot 0.1%, excipients and water to 100%.
- In the aqueous step a), performed at a temperature of approximately 40°C, the following compounds are mixed together: phytic acid, lipoic acid, vitamin E, vitamin A, vitamin C, quercetin, reduced L-glutathione, cetraria islandica, green tea, vitis vinifera (resveratrol), gluconolactone, M.S.M., melilot. Preferably at least two of the following compounds, phytic acid, lipoic acid, vitamin E, vitamin A, vitamin C, quercetin, reduced L-glutathione, cetraria islandica, green tea, vitis vinifera (resveratrol), gluconolactone, M.S.M., melilot and even more preferably the following phytic acid, lipoic acid, vitamin E, vitamin A, vitamin C, quercetin, reduced L-glutathione, cetraria islandica, green tea, vitis vinifera (resveratrol), gluconolactone, M.S.M., melilot.
- Step a) is then followed by the fatty step b) which is performed at a temperature of approximately 70°C. During this phase the excipients suited to the formulation according to the known art are added to the reaction mixture.
- The last step in the process, step c), is the cooling step, performed at a temperature of approximately 30°C. In this step c), the lactoferrin associated with nanolipids is added to the reaction mixture as obtained from the preceding steps a) and b).
- The resulting final composition is a cream with pH of 6, after the addition of an appropriate quantity of triethanolamine.
Claims (7)
- Use of a composition based on natural chelating substances which consists of lactoferrin carried by association with nanolipids which are particles having a structure analogous to the cell membranes, with a diameter of less than 250 nm as active ingredient for the preparation of a medicament for the topical treatment of pathologies characterized by heavy metal accumulation.
- Use of the composition according to claim 1 for the preparation of a medicament for the topical treatment of cutaneous dyschromias.
- Use of the composition according to claims 1 or 2, characterized in that said Lactoferrin is in a concentration between 1% and 20% w/w of the total composition.
- Use of the composition according to claim 3, characterized in that said nanolipid associated Lactoferrin is present in a concentration between 3% and 12% more preferably between 5% and 9% w/w of the total composition.
- Use of the composition according to claim 4, characterized in that said Lactoferrin is present in a concentration between 5% and 9% w/w of the total composition.
- Use of the composition according to claim 5, characterized in that said Lactoferrin is present in a concentration of 6% w/w of the total composition.
- Composition based on natural chelating substances consisting of lactoferrin carried by association with nanolipids which are particles having a structure analogous to the cell membranes, with a diameter of less than 250 nm as active ingredient for use in the topical treatment of pathologies characterized by heavy metal accumulation, cutaneous dyschromias, ecchymotic pigmentations.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITMI2008A001285A IT1394514B1 (en) | 2008-07-15 | 2008-07-15 | NEW COMPOSITION FOR THE TREATMENT OF ECCHIMOTICS PIGMENTATION |
PCT/IB2009/006222 WO2010007494A2 (en) | 2008-07-15 | 2009-07-13 | New composition for the treatment of ecchymotic pigmentations |
Publications (2)
Publication Number | Publication Date |
---|---|
EP2323625A2 EP2323625A2 (en) | 2011-05-25 |
EP2323625B1 true EP2323625B1 (en) | 2016-07-13 |
Family
ID=40670928
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP09740732.4A Active EP2323625B1 (en) | 2008-07-15 | 2009-07-13 | New composition for the treatment of ecchymotic pigmentations |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP2323625B1 (en) |
DK (1) | DK2323625T3 (en) |
ES (1) | ES2595368T3 (en) |
IT (1) | IT1394514B1 (en) |
PL (1) | PL2323625T3 (en) |
PT (1) | PT2323625T (en) |
WO (1) | WO2010007494A2 (en) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102232908A (en) * | 2010-04-30 | 2011-11-09 | 李德远 | Nutritional protection cream for resisting dinitrogen tetroxide |
ITMI20121356A1 (en) * | 2012-08-01 | 2014-02-02 | Biagio Biancardi | APOLATTOFERRINA FOR THE TREATMENT OF IRON ACCUMULATION PATHOLOGIES |
EP4137511A4 (en) | 2020-04-16 | 2024-01-10 | Dermopartners S L | New composition for use to treat and prevent infections by covid-19 and other coronaviruses |
IT202000009430A1 (en) | 2020-04-29 | 2021-10-29 | Tdc Tech Dedicated To Care Srl | COMPOSITION FOR THE PREVENTION AND/OR TREATMENT OF RESPIRATORY TRACT INFECTIONS |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2641696B2 (en) * | 1986-04-11 | 1991-03-08 | Sederma Sa | USE OF A MIXTURE CONTAINING LACTOFERRIN IN FREE ANTI-RADICAL COSMETIC PREPARATIONS |
US20040214750A1 (en) * | 2003-04-28 | 2004-10-28 | Georgiades Izolda M. | Medicaments for healing skin conditions in humans |
US20070264222A1 (en) * | 2006-05-10 | 2007-11-15 | Biohealth Advance, Llc | Enhanced protection against skin injury in humans |
-
2008
- 2008-07-15 IT ITMI2008A001285A patent/IT1394514B1/en active
-
2009
- 2009-07-13 PT PT97407324T patent/PT2323625T/en unknown
- 2009-07-13 WO PCT/IB2009/006222 patent/WO2010007494A2/en active Application Filing
- 2009-07-13 DK DK09740732.4T patent/DK2323625T3/en active
- 2009-07-13 EP EP09740732.4A patent/EP2323625B1/en active Active
- 2009-07-13 ES ES09740732.4T patent/ES2595368T3/en active Active
- 2009-07-13 PL PL09740732T patent/PL2323625T3/en unknown
Also Published As
Publication number | Publication date |
---|---|
ITMI20081285A1 (en) | 2010-01-16 |
PL2323625T3 (en) | 2017-01-31 |
DK2323625T3 (en) | 2016-10-03 |
IT1394514B1 (en) | 2012-07-05 |
PT2323625T (en) | 2016-10-19 |
ES2595368T3 (en) | 2016-12-29 |
EP2323625A2 (en) | 2011-05-25 |
WO2010007494A2 (en) | 2010-01-21 |
WO2010007494A3 (en) | 2010-03-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP2320919B1 (en) | Large-scale process for the preparation of thylakoids | |
US20080113921A1 (en) | Use of a Compound Comprising D-Mannoheptulose and/or Perseitol for Treating and Preventing Innate Immunity Modification Diseases | |
EP1494692A1 (en) | Topical pharmaceutical compositions comprising proanthocyanidins for the treatment of dermatitis | |
CA2821876A1 (en) | Avocado flesh and/or skin extract rich in polyphenols and cosmetic, dermatological and nutraceutical compositions comprising same | |
EP2323625B1 (en) | New composition for the treatment of ecchymotic pigmentations | |
JP2004346045A (en) | Cosmetic additive, bathing agent and health food containing sake lees extract obtained in brewing of sake using deep seawater | |
CN110623885A (en) | Anti-glycosylation yellow-dispelling and anti-aging composition and preparation method and application thereof | |
JP5542143B2 (en) | A. INDICA and M.C. CHARANTIA or S.C. External composition containing an extract of INDICUM | |
JP2588723B2 (en) | Hair cosmetics | |
KR102309913B1 (en) | Composition for improving hangover cure and alcoholic liver injury comprising root extract of Rosa multiflora THUNB | |
EP2692355B1 (en) | Apolactoferrin for the treatment of iron accumulation diseases | |
JP4325908B2 (en) | Lipolysis accelerator, skin external preparation and food and drink using the same | |
JP3940509B2 (en) | Topical skin preparation | |
WO2009155097A1 (en) | Natural product inhibitors of 3dg | |
KR20230154821A (en) | Bertolletia excelsa extract and uses thereof | |
KR100860272B1 (en) | Method for extraction and purification of effective component from agrimonia pilosa ledeb and crude drug composition containing extract thereof for prevention and treatment of pimple | |
RU2469704C1 (en) | Regenerin serum for external application with anti-inflammatory and regenerative effect | |
JP2010241779A (en) | Skin care preparation for external use for ameliorating rough skin | |
JP5548379B2 (en) | Antihistamine containing pollen cargo | |
JPH1171292A (en) | Preparation for external use for skin | |
JP4786028B2 (en) | Antiallergic agent | |
JP7455350B2 (en) | Damage inhibitors, cosmetics, and food and beverages caused by air pollutants | |
US7078437B2 (en) | Apolipoprotein D degradation inhibitor | |
JPH11180850A (en) | Cosmetic | |
KR20170094609A (en) | Manufactureing method of periodontitis prevention solution |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20110210 |
|
AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR |
|
AX | Request for extension of the european patent |
Extension state: AL BA RS |
|
DAX | Request for extension of the european patent (deleted) | ||
17Q | First examination report despatched |
Effective date: 20111206 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R079 Ref document number: 602009039705 Country of ref document: DE Free format text: PREVIOUS MAIN CLASS: A61K0009127000 Ipc: A61P0017000000 |
|
GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
|
RIC1 | Information provided on ipc code assigned before grant |
Ipc: A61K 9/00 20060101ALI20160126BHEP Ipc: A61P 17/00 20060101AFI20160126BHEP Ipc: A61K 38/40 20060101ALI20160126BHEP Ipc: A61K 9/127 20060101ALI20160126BHEP |
|
INTG | Intention to grant announced |
Effective date: 20160219 |
|
GRAS | Grant fee paid |
Free format text: ORIGINAL CODE: EPIDOSNIGR3 |
|
GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR |
|
REG | Reference to a national code |
Ref country code: GB Ref legal event code: FG4D |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: REF Ref document number: 811816 Country of ref document: AT Kind code of ref document: T Effective date: 20160715 Ref country code: CH Ref legal event code: EP |
|
REG | Reference to a national code |
Ref country code: IE Ref legal event code: FG4D |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 8 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R096 Ref document number: 602009039705 Country of ref document: DE |
|
REG | Reference to a national code |
Ref country code: NL Ref legal event code: FP |
|
REG | Reference to a national code |
Ref country code: DK Ref legal event code: T3 Effective date: 20160926 |
|
REG | Reference to a national code |
Ref country code: SE Ref legal event code: TRGR |
|
REG | Reference to a national code |
Ref country code: PT Ref legal event code: SC4A Ref document number: 2323625 Country of ref document: PT Date of ref document: 20161019 Kind code of ref document: T Free format text: AVAILABILITY OF NATIONAL TRANSLATION Effective date: 20161012 |
|
REG | Reference to a national code |
Ref country code: LT Ref legal event code: MG4D |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: NV Representative=s name: FABIANO, FRANKE AND MGT SAGL, CH |
|
REG | Reference to a national code |
Ref country code: NO Ref legal event code: T2 Effective date: 20160713 |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2595368 Country of ref document: ES Kind code of ref document: T3 Effective date: 20161229 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: BE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160731 |
|
REG | Reference to a national code |
Ref country code: RO Ref legal event code: EPE |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: FI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: IS Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20161113 Ref country code: HR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: LT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 |
|
REG | Reference to a national code |
Ref country code: GR Ref legal event code: EP Ref document number: 20160401991 Country of ref document: GR Effective date: 20161118 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LV Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: BE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R097 Ref document number: 602009039705 Country of ref document: DE |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: EE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: MC Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 |
|
REG | Reference to a national code |
Ref country code: IE Ref legal event code: MM4A |
|
PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SM Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: SK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: CZ Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 Ref country code: BG Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20161013 |
|
26N | No opposition filed |
Effective date: 20170418 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 9 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160713 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160713 Ref country code: SI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: HU Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO Effective date: 20090713 Ref country code: CY Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: MT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160731 Ref country code: MK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160713 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 10 |
|
REG | Reference to a national code |
Ref country code: NL Ref legal event code: PD Owner name: TDC TECHNOLOGY DEDICATED TO CARE S.R.L.; IT Free format text: DETAILS ASSIGNMENT: CHANGE OF OWNER(S), ASSIGNMENT; FORMER OWNER NAME: BIANCARDI, BIAGIO Effective date: 20180717 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PUE Owner name: TDC TECHNOLOGY DEDICATED TO CARE S.R.L., IT Free format text: FORMER OWNER: BIANCARDI, BIAGIO, IT |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R082 Ref document number: 602009039705 Country of ref document: DE Representative=s name: GODEMEYER BLUM LENZE PATENTANWAELTE, PARTNERSC, DE Ref country code: DE Ref legal event code: R081 Ref document number: 602009039705 Country of ref document: DE Owner name: TDC TECHNOLOGY DEDICATED TO CARE S.R.L., IT Free format text: FORMER OWNER: BIAGIO, BIANCARDI, NAPOLI, IT |
|
REG | Reference to a national code |
Ref country code: GB Ref legal event code: 732E Free format text: REGISTERED BETWEEN 20180712 AND 20180718 |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: PC2A Effective date: 20180807 Ref country code: ES Ref legal event code: PC2A Owner name: TDC TECHNOLOGY DEDICATED TO CARE S.R.L. Effective date: 20180807 |
|
REG | Reference to a national code |
Ref country code: NO Ref legal event code: CHAD Owner name: TDC TECHNOLOGY DEDICATED TO CARE S.R.L., IT |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: TP Owner name: TDC TECHNOLOGY DEDICATED TO CARE S.R.L., IT Effective date: 20181025 |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: PC Ref document number: 811816 Country of ref document: AT Kind code of ref document: T Owner name: TDC TECHNOLOGY DEDICATED TO CARE S.R.L., IT Effective date: 20190115 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PCAR Free format text: NEW ADDRESS: PIAZZETTA SAN CARLO 2, 6900 LUGANO (CH) |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: UEP Ref document number: 811816 Country of ref document: AT Kind code of ref document: T Effective date: 20160713 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: CH Payment date: 20200616 Year of fee payment: 12 Ref country code: TR Payment date: 20200520 Year of fee payment: 12 Ref country code: DK Payment date: 20200522 Year of fee payment: 12 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: SE Payment date: 20200522 Year of fee payment: 12 Ref country code: NL Payment date: 20200617 Year of fee payment: 12 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: NO Payment date: 20200702 Year of fee payment: 12 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: AT Payment date: 20200623 Year of fee payment: 12 |
|
REG | Reference to a national code |
Ref country code: DK Ref legal event code: EBP Effective date: 20210731 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL Ref country code: NO Ref legal event code: MMEP |
|
REG | Reference to a national code |
Ref country code: NL Ref legal event code: MM Effective date: 20210801 |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: MM01 Ref document number: 811816 Country of ref document: AT Kind code of ref document: T Effective date: 20210713 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LI Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20210731 Ref country code: CH Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20210731 Ref country code: AT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20210713 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20210714 Ref country code: NO Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20210731 Ref country code: NL Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20210801 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: DK Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20210731 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: RO Payment date: 20230612 Year of fee payment: 15 Ref country code: PT Payment date: 20230601 Year of fee payment: 15 Ref country code: FR Payment date: 20230614 Year of fee payment: 15 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: PL Payment date: 20230614 Year of fee payment: 15 Ref country code: GR Payment date: 20230607 Year of fee payment: 15 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: IT Payment date: 20230712 Year of fee payment: 15 Ref country code: GB Payment date: 20230712 Year of fee payment: 15 Ref country code: ES Payment date: 20230801 Year of fee payment: 15 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: DE Payment date: 20230728 Year of fee payment: 15 |